The role of measurement uncertainty in Health Technology Assessments (HTAs) of in-vitro tests

Introduction: Numerous factors contribute to uncertainty in test measurement procedures, and this uncertainty can impact on the downstream clinical utility and cost-effectiveness of testing strategies. Currently however, there is no clear guidance concerning if or how such factors should be considered within Health Technology Assessments (HTAs) of tests. Aim: To provide an introduction to key concepts in measurement uncertainty and explore, via systematic review, current methods utilised within HTAs for the assessment of measurement uncertainty. Methods: HTAs of in-vitro tests including a model-based economic evaluation were identified via the Centre for Reviews and Dissemination (CRD) HTA database, HTA authority websites and citation checking. Data extraction was conducted to explore the specific components of measurement uncertainty assessed and methods utilised, and results were narratively synthesised.Results: Of 107 identified HTAs, 20 (19%) attempted to assess components of measurement uncertainty: 15 included an ‘intermediate’ assessment (e.g. literature review or laboratory survey); 4 also included components within the economic model; and 1 considered measurement uncertainty within the model only. The specific components assessed and methods adopted differed across studies. In particular, several techniques were employed within the economic models to incorporate data on test agreement, total error or biological and analytical variability. Conclusion: Various approaches have been adopted within a minority of HTAs to attempt to capture the impact of measurement uncertainty on test outcomes; uncertainty remains around when such assessments are required and appropriate methodology for conducting analyses, particular within economic evaluations.